Toward A variable RBE for proton beam therapy.

Area of Science:

• Radiation oncology
• Medical physics
• Cancer genomics

Background:

• Proton beam therapy (PBT) currently uses a generic relative biological effectiveness (RBE) of 1.1 for human cancers and normal tissues.
• The current RBE is not based on extensive tumor models or clinically relevant endpoints for organs at risk.
• Inter-tumoral genomic heterogeneity influences cancer treatment response, with DNA repair pathway defects potentially increasing RBE.

Purpose of the Study:

• To review experimental data on DNA damage repair impacting RBE values and biophysical modeling for PBT.
• To explore the potential for predicting variable RBE values to personalize PBT for individual patients.
• To discuss approaches for therapeutically exploiting PBT's biological advantages and mitigating treatment toxicity.

Main Methods:

• Review of experimental data on proton damage to DNA and its impact on RBE.
• Examination of in vitro and in vivo experimental approaches for studying proton sensitivity.
• Discussion of recent clinical findings related to PBT and RBE variations.

Main Results:

• Defects in DNA repair pathways in cancer subsets are associated with increased RBE in vitro.
• Limited in vivo and clinical data currently confirm increased RBE values in human cancers.
• Evidence for variable RBE in normal tissue toxicity is sparse and conflicting.

Conclusions:

• Predicting variable RBE values could enable personalized PBT, selecting patients with proton-sensitive cancers and potentially de-escalating doses to reduce normal tissue toxicity.
• Identifying RBE biomarkers could lead to biologically optimized therapies for enhanced local control and better understanding/prevention of PBT-associated toxicities.
• Further research into the biological effects of protons is crucial for advancing PBT's clinical application and improving patient outcomes.